DESCRIPTION (APPLICANT'S ABSTRACT): A majority of Americans are overweight and 33% of our population is classified as obese. Ephedrine and related analogs are the major active components of Ephedra or ma huang (Ephedra sinica) herbal products that are proposed to cause weight loss. The mechanism of this effect is not well understood. The beneficial and adverse effects of ephedrine, including Ephedra herbal products are linked to interactions with alpha and beta-adrenergic receptors. Many of the previous pharmacological studies with ephedrine and Ephedra occurred prior to the discovery of cloned human adrenergic receptor subtypes. This project plans to systematically examine the pharmacological properties (receptor affinities and functional effects) of the compounds in herbal products on subtypes of human alpha- (alpha2a, alpha2b, alpha2c and alphala, alphalb and alphad) and beta-(beta1, beta2 and beta3) adrenergic receptors. The specifc aims are as follows: 1) To collect Ephedra samples, and through solvent extraction and chromatographic techniques, separate these preparations into fractions for biological testing. Active constituents in the fractions will be isolated, purified and characterized; and 2) To establish the binding potency, and functional activities of isolated compounds on human alpha- and beta-adrenergic receptors that are expressed in CHO, HEK and PAZ-6 cells. With the multiplicity of adrenergic receptor subtypes discovered, it will be important to establish the pharmacological adrenergic receptor selectivity (either as an agonist or antagonist) for each of the isolated Ephedra compounds. These studies will determine whether ephedrine alkaloids, or other components contribute to adverse and beneficial effects associated with herbal Ephedra use. Due to the abuse potential, it is clear that the evaluation of the safety and effectiveness of Ephedra herbal products needs greater scrutiny, and results of these studies will provide an understanding of the molecular and cellular basis for extrapolation to their observed in vivo actions.